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      Reversal of Established Nephropathy in New Zealand B/W F 1Mice by 15-Deoxyspergualin

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          Abstract

          The therapeutic effect of 15-deoxyspergualin (DSP) in old New Zealand Black/White F<sub>1</sub> mice (B/W mice) with clinical nephropathy was studied and compared with cyclophosphamide (CY). The mice were treated with 0.05 ml phosphate-buffered saline, subcutaneously, four times/week, with DSP, 6 mg/kg body weight, s.c, four times/week, or with CY, 15 mg/kg, i.p., once a week, starting at the 28th week of age. They were serially semiquantitated for proteinuria, and serum IgG anti-dsDNA antibody was measured by ELISA. Spleen cell surface markers such as L3T4, Lyt 2 and IgG were flow-cytometrically analyzed, and interleukin-2 (IL-2) activity in vitro was measured using CTLL cells. Kidney specimens were studied with light and immunofluorescence microscopy. The mice treated with either CY or DSP survived significantly longer than the control mice. L3T4<sup>+</sup> cells in the DSP-treated mice at 40 weeks of age were significantly less than those in the 28-week-old control mice (p < 0.05). In contrast, IL-2 generation in the three groups of mice showed no significant variations at 32–40 weeks of age. Serum anti-DNA antibody levels in both of the CY and DSP groups remained low and comparable with that in the 28-week-old mice, and the incidence of significant proteinuria decreased. Likewise, glomerular histology in the treated groups was improved compared with the 28-week-old control mice, and the deposition of IgG and C3 in the treated groups remained unchanged or further decreased. Accordingly, the renal (immuno)histological findings in the DSP group were quite comparable with or even better than those in the CY-treated mice. DSP may have suppressed the abnormal antibody production by modulating the T cell function(s), which is in contrast to the direct action against B cells due to CY.

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          Author and article information

          Journal
          NEF
          Nephron
          10.1159/issn.1660-8151
          Nephron
          S. Karger AG
          1660-8151
          2235-3186
          1991
          1991
          11 December 2008
          : 57
          : 1
          : 99-105
          Affiliations
          Department of Medicine, Kitasato University School of Medicine, and Kitasato Biochemical Laboratories, Sagamihara; Department of Microbiology, Tokyo Women’s Medical College, and Institute of Microbial Chemistry, Tokyo, Japan
          Article
          186225 Nephron 1991;57:99–105
          10.1159/000186225
          2046819
          © 1991 S. Karger AG, Basel

          Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

          Page count
          Pages: 7
          Categories
          Original Paper

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